Determinants of Bioartificial Myocardial Graft Survival and Engraftment In Vivo

Abstract

The specific interactions between tissue-engineered grafts and host tissue are frequently neglected. The aim of this study was to describe and quantify the fate of a tissue-engineered cardiac graft in vivo. Neonatal rat cardiomyocytes were cast into a collagen mesh, forming a bioartificial myocardial tissue (AMT). After 7 days in vitro, four groups were formed (Group A: sham; Group B: matrix; Group C: AMT [with additional host treatment with cyclosporine and prednisolone]; Group D: AMT; each n = 5) and the tissue grafts were implanted into the muscle pouch of adult rats at 14, 21 and 28 days. Implants were stained for troponin-T, BrdU, MF-20, desmin, vimentin, Flk-1, CD8, CD4, pentachrome, PSR and H&E. AMT cell count, cell proportion, contractility, viability and metabolism proved stable in vitro. Grafted cells decreased over time and were detected in Group C until the end of the experiment (Day 28), and in Group D until Day 21. Angiogenesis began at the peripheries and slowly progressed toward the cores of the grafts. The thickness and collagen content of the matrix remained stable in Group C for 14 days, and decreased in all groups until Day 28 (thickness: Group B, -66%; Group C, -50%; Group D, -100%). Grafts were predominately infiltrated by macrophages and stromal cells, and less so by lymphocytes (Group D > B > C). The differentiation of cardiac and non-cardiac grafted cells, infiltrating cells, scaffold kinetics and angiogenesis showed host immune responses and degree of angiogenesis to be the determinants for AMT graft survival.